Stretch‐Induced Increase in Cardiac Contractility Is Independent of Myocyte Ca2+ While Block of Stretch Channels by Streptomycin Improves Contractility After Ischemic Stunning

Authors

Samhita S. Rhodes, Medical College of Wisconsin
Amadou KS Camara, Medical College of Wisconsin
Mohammed Aldakkak, Medical College of Wisconsin
James S. Heisner, Medical College of Wisconsin
David F. Stowe, Marquette University

Document Type

Article

Language

eng

Publication Date

8-18-2015

Publisher

Wiley

Source Publication

Physiological Reports

Source ISSN

2051-817X

Original Item ID

DOI: 10.14814/phy2.12486

Abstract

Stretching the cardiac left ventricle (LV) enhances contractility but its effect on myoplasmic [Ca²⁺] is controversial. We measured LV pressure (LVP) and [Ca²⁺] as a function of intra-LV stretch in guinea pig intact hearts before and after 15 min global stunning ± perfusion with streptomycin (STM), a stretch activated channel blocker. LV wall [Ca²⁺] was measured by indo-1 fluorescence and LVP by a saline-filled latex balloon inflated in 50 μL steps to stretch the LV. We implemented a mathematical model to interpret crossbridge dynamics and myofilament Ca²⁺ responsiveness from the instantaneous relationship between [Ca²⁺] and LVP ± stretching. We found that: (1) stretch enhanced LVP but not [Ca²⁺] before and after stunning in either control (CON) and STM groups, (2) after stunning [Ca²⁺] increased in both groups although higher in STM versus CON (56% vs. 39%), (3) STM-enhanced LVP after stunning compared to CON (98% vs. 76% of prestunning values), and (4) stretch-induced effects on LVP were independent of [Ca²⁺] before or after stunning in both groups. Mathematical modeling suggested: (1) cooperativity in cross-bridge kinetics and myofilament Ca²⁺ handling is reduced after stunning in the unstretched heart, (2) stunning results in depressed myofilament Ca²⁺ sensitivity in the presence of attached cross-bridges regardless of stretch, and (3) the initial mechanism responsible for increased contractility during stretch may be enhanced formation of cross-bridges. Thus stretch-induced enhancement of contractility is not due to increased [Ca²⁺], whereas enhanced contractility after stunning in STM versus CON hearts results from improved Ca²⁺ handling and/or enhanced actinomyosin cross-bridge cycling.

Comments

Accepted version. Physiological Reports, Vol 3, No. 8 (August 18, 2015): e12486. DOI. © 2015 Wiley and The Physiological Society. Used with permission.

Recommended Citation

Rhodes, Samhita S.; Camara, Amadou KS; Aldakkak, Mohammed; Heisner, James S.; and Stowe, David F., "Stretch‐Induced Increase in Cardiac Contractility Is Independent of Myocyte Ca2+ While Block of Stretch Channels by Streptomycin Improves Contractility After Ischemic Stunning" (2015). Biomedical Engineering Faculty Research and Publications. 422.
https://epublications.marquette.edu/bioengin_fac/422